Reproducibility of fibrous cap status assessment of carotid artery plaques by contrast-enhanced MRI.

BACKGROUND AND PURPOSE: Reproducibility in identifying the fibrous cap (FC) of carotid artery plaques by noncontrast-enhanced MRI has been shown to be poor. The objective of this study was to assess the reproducibility of multisequence MRI, including contrast-enhanced images, in assessing FC status. METHODS: Forty-five symptomatic patients with 30% to 69% carotid artery stenosis underwent a multisequence MRI protocol, which included contrast-enhanced images. FC status (ie, discrimination between fibrotic and/or calcified plaques, plaques with a lipid-rich necrotic core and an intact and thick FC, and plaques with a lipid-rich necrotic core and a thin and/or ruptured FC) was independently assessed by 3 observers of which one also scored all images on a different occasion. Linear weighted kappa coefficients (kappa) were calculated as indicators of inter- and intraobserver agreement. RESULTS: On a per-slice basis, interobserver agreement was good (kappa=0.60, 0.64, and 0.71), whereas intraobserver agreement was very good (kappa=0.86). On a per-plaque basis, interobserver agreement was good (kappa=0.64, 0.69, and 0.78), whereas intraobserver agreement was very good (kappa=0.96). CONCLUSIONS: This study found good interobserver and very good intraobserver agreement in assessing FC status of carotid artery plaques. Future studies are warranted to determine the predictive value of FC status assessment by multisequence MRI, including contrast-enhanced images, on the occurrence of (recurrent) cerebral ischemic events.

Atherosclerosis: contrast-enhanced MR imaging of vessel wall in rabbit model--comparison of gadofosveset and gadopentetate dimeglumine.

PURPOSE: To investigate the potential of gadofosveset for contrast material-enhanced magnetic resonance (MR) imaging of plaque in a rabbit model of atherosclerosis. MATERIALS AND METHODS: All experiments were approved by the animal ethics committee. Thirty-one New Zealand White rabbits were included in one of four study groups: animals with atherosclerosis imaged with gadofosveset (n = 10) or gadopentetate dimeglumine (n = 7) and control animals imaged with gadofosveset (n = 7) or gadopentetate dimeglumine (n = 7). Aortic atherosclerosis was induced through endothelial denudation combined with a cholesterol-enriched diet. Control rabbits underwent a sham surgical procedure and received a regular diet. After 8 weeks, pre- and postcontrast T1-weighted MR images of the aortic vessel wall were acquired. Relative signal enhancement was determined with dedicated software. Statistical analysis was performed by using a generalized linear mixed model. Immunohistochemical staining with CD31 and albumin was used to assess microvessel density and the albumin content of the vascular wall. Group differences were analyzed by using a chi(2) test. Gadofosveset spatial distribution and content within the vessel wall were determined with proton-induced x-ray emission (PIXE) analysis. RESULTS: Postcontrast signal enhancement was significantly greater for atherosclerotic than for control animals imaged with gadofosveset (P = .022). Gadopentetate dimeglumine could not enable discrimination between normal and atherosclerotic vessel walls (P = .428). PIXE analysis showed higher amounts of gadopentetate dimeglumine than gadofosveset in both atherosclerotic and normal rabbit aortas. Immunohistochemical staining revealed the presence of albumin and increased microvessel density in the vascular walls of atherosclerotic rabbits. CONCLUSION: These results suggest that gadofosveset can be used to differentiate between atherosclerotic and normal rabbit vessel walls. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/250/3/682/DC1.

Clinical perspectives of hybrid proton-fluorine magnetic resonance imaging and spectroscopy.

The number of applications of fluorine 19 (19F) magnetic resonance (MR) imaging and spectroscopy in biomedical and clinical research is steadily growing. The 100% natural abundance of fluorine and its relatively high sensitivity for MR (83% to that of protons) make it an interesting nucleus for a wide range of MR applications. Fluorinated contrast media have a number of advantages over the conventionally used gadolinium-based or iron-based contrast agents. The absence of an endogenous fluorine background intensity in the human body facilitates reliable quantification of fluorinated contrast medium or drugs. Anatomy can be visualized separately with proton MR imaging, creating the application of hybrid hydrogen 1 (1H)/19F MR imaging. The availability of 2 channels (ie, the 1H and 19F channels) enables dual-targeted molecular imaging. Recently, novel developments have emerged on fluorine-based contrast media in preclinical studies and imaging techniques. The developments in fluorine MR seem promising for clinical applications, with contributions in therapy monitoring, assessment of lung function, angiography, and molecular imaging. This review outlines the translation from recent advances in preclinical MR imaging and spectroscopy to future perspectives of clinical hybrid 1H/19/F MR imaging applications.

Gadofosveset-enhanced magnetic resonance imaging of human carotid atherosclerotic plaques: a proof-of-concept study.

OBJECTIVE: To investigate the potential of gadofosveset-enhanced MR imaging for the characterization of human carotid atherosclerotic plaques. MATERIALS AND METHODS: Sixteen (9 symptomatic, 7 asymptomatic) patients with 70% to 99% carotid stenosis (according to NASCET criteria) were included (13 men, 3 women, mean age 67.6 years). All patients underwent baseline precontrast MR imaging of the carotid plaque. Immediately after completion of the baseline examination, 0.03 mmol/kg gadofosveset was administered. At 24 hours postinjection, the acquisition was repeated. Twelve patients were scheduled for carotid endarterectomy. Carotid endarterectomy specimens were HE-, CD31-, CD68-, and albumin-stained to correlate signal enhancement with plaque composition, intraplaque microvessel density, and macrophage and albumin content. A random intercept model was used to compare signal enhancement between symptomatic and asymptomatic patients, adjusting for size of various plaque components. This study was approved by the institutional medical ethics committee. All participants gave written informed consent. RESULTS: Signal enhancement (SE) of the plaque was significantly higher in symptomatic patients compared with asymptomatic patients (median log SE 0.182 vs. -0.109, respectively, P < 0.001). A positive association (as expressed by a regression coefficient beta = 0.0035) was found between signal enhancement on the log scale and intraplaque albumin content (P = 0.038). There was no association between signal enhancement and various other plaque components. CONCLUSION: In this study, the potential of gadofosveset-enhanced human carotid plaque MR imaging for identification of high-risk plaques was demonstrated. Signal enhancement of the plaque after administration of gadofosveset was associated with differences in intraplaque albumin content. Although promising, we emphasize that these results are based on a small patient population. Larger prospective studies are warranted.

Impaired skeletal muscle substrate oxidation in glucose-intolerant men improves after weight loss.

OBJECTIVE: An impaired fatty acid handling in skeletal muscle may be involved in the development of insulin resistance and diabetes mellitus type 2 (DM2). We investigated muscle fatty acid metabolism in glucose-intolerant men (impaired glucose tolerance (IGT)), a prediabetic state, relative to BMI-matched control men (normal glucose tolerance (NGT)) during fasting and after a meal, because most people in the western society are in the fed state most of the day. METHODS AND PROCEDURES: Skeletal muscle free fatty acid (FFA) uptake and oxidation were studied using the stable isotope tracer [2,2-(2)H]-palmitate and muscle indirect calorimetry in the forearm model during fasting and after a mixed meal (33 energy % (E%) carbohydrates, 61 E% fat). Intramyocellular triglycerides (IMTGs) were monitored with 1H-magnetic resonance spectroscopy. IGT men were re-examined after weight loss (-15% of body weight (BW)). RESULTS: The postprandial increase in forearm muscle respiratory quotient (RQ) was blunted in IGT compared to NGT, but improved after weight loss. Weight loss also improved fasting-fat oxidation and tended to decrease IMTGs (P=0.08). No differences were found in fasting and postprandial forearm muscle fatty acid uptake between NGT and IGT, or in IGT before and after weight loss. DISCUSSION: The ability to switch from fat oxidation to carbohydrate oxidation after a meal is already impaired in the prediabetic state, suggesting this may be an early factor in the development toward DM2. This impaired ability to regulate fat oxidation during fasting and after a meal (impaired metabolic flexibility) can be (partly) reversed by weight loss.